Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity.
Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity.
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DOI：
10.1016/j.virol.2009.07.018
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发表时间：
2009-10-10
期刊：
影响因子：
3.7
通讯作者：
Jiang, Shibo
中科院分区：
文献类型：
--
作者：
Du, Lanying;Zhao, Guangyu;Chan, Chris C. S.;Sun, Shihui;Chen, Min;Liu, Zhonghua;Guo, Hongxiang;He, Yuxian;Zhou, Yusen;Zheng, Bo-Jian;Jiang, Shibo
严重急性呼吸综合征(SARS)是一种新出现的传染病。这种疾病可能会从动物宿主中复发，这突显了开发安全有效的疫苗以防止未来SARS疫情的重要性。在本研究中，我们分别在哺乳动物(293T)细胞、昆虫(Sf9)细胞和大肠杆菌中表达了重组受体结合域(RRBD)，并在建立的小鼠模型中比较了它们的免疫原性和对SARS-CoV感染的保护作用。我们的结果表明，在上述系统中表达的rRBD蛋白都保持了完整的构象，能够诱导高效的中和抗体应答和对SARS冠状病毒攻击的完全保护性免疫，尽管在293T细胞中表达的rRBD蛋白诱导了更强的体液免疫应答，中和活性显著高于在Sf9和大肠杆菌中表达的rRBD蛋白(P<0.05)。这些结果表明，三种rRBD均能有效地诱导免疫应答和保护SARS-CoV，上述表达系统均可用于生产基于rRBD的SARS亚单位疫苗。在非人类灵长类动物SARS模型中，将优先考虑在哺乳动物细胞中表达的rRBD，因为它比在大肠杆菌和昆虫细胞中表达的更容易折叠成自然构象，并诱导更高水平的中和抗体反应，因此将优先用于未来的疫苗效力评估。
Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease. The potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future SARS epidemic. In this study, we expressed the recombinant receptor-binding domain (rRBD) in mammalian (293T) cells, insect (Sf9) cells, and E. coli, respectively, and compared their immunogenicity and protection against SARS-CoV infection in an established mouse model. Our results show that all rRBD proteins expressed in the above systems maintained intact conformation, being able to induce highly potent neutralizing antibody responses and complete protective immunity against SARS-CoV challenge in mice, albeit the rRBD expressed in 293T cells elicited stronger humoral immune responses with significantly higher neutralizing activity (P < 0.05) than those expressed in Sf9 and E. coli cells. These results suggest that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rRBD-based SARS subunit vaccines. Preference will be given to rRBD expressed in mammalian cells for future evaluation of the vaccine efficacy in a non-human primate model of SARS because of its ability to refold into a native conformation more readily and to induce higher level of neutralizing antibody responses than those expressed in E. coli and insect cells.
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影响因子：
5.5
作者：
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通讯作者：
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作者：
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作者：
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DOI：
10.1016/j.bbrc.2009.05.003
发表时间：
2009-07-10
影响因子：
3.1
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2004.09.106
发表时间：
2004-11-12
影响因子：
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作者：
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